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Sci Transl Med ; 5(172): 172ra20, 2013 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-23408053

RESUMO

Although many human cancers are located in mucosal sites, most cancer vaccines are tested against subcutaneous tumors in preclinical models. We therefore wondered whether mucosa-specific homing instructions to the immune system might influence mucosal tumor outgrowth. We showed that the growth of orthotopic head and neck or lung cancers was inhibited when a cancer vaccine was delivered by the intranasal mucosal route but not the intramuscular route. This antitumor effect was dependent on CD8⁺ T cells. Indeed, only intranasal vaccination elicited mucosal-specific CD8⁺ T cells expressing the mucosal integrin CD49a. Blockade of CD49a decreased intratumoral CD8⁺ T cell infiltration and the efficacy of cancer vaccine on mucosal tumor. We then showed that after intranasal vaccination, dendritic cells from lung parenchyma, but not those from spleen, induced the expression of CD49a on cocultured specific CD8⁺ T cells. Tumor-infiltrating lymphocytes from human mucosal lung cancer also expressed CD49a, which supports the relevance and possible extrapolation of these results in humans. We thus identified a link between the route of vaccination and the induction of a mucosal homing program on induced CD8⁺ T cells that controlled their trafficking. Immunization route directly affected the efficacy of the cancer vaccine to control mucosal tumors.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/administração & dosagem , Quimiotaxia de Leucócito , Neoplasias de Cabeça e Pescoço/terapia , Imunidade nas Mucosas , Neoplasias Pulmonares/terapia , Mucosa Nasal/imunologia , Vacinas contra Papillomavirus/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Administração Intranasal , Animais , Antígenos CD/metabolismo , Vacinas Anticâncer/imunologia , Proliferação de Células , Células Cultivadas , Células Dendríticas/imunologia , Feminino , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Injeções Intramusculares , Cadeias alfa de Integrinas/metabolismo , Integrina alfa1/metabolismo , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Linfonodos/imunologia , Linfócitos do Interstício Tumoral/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Vacinas contra Papillomavirus/imunologia , Toxinas Shiga/administração & dosagem , Baço/imunologia , Carga Tumoral
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